O27 Ch3

Structure I Spironolactone are almost planar and perpendicular to the E ring and to the 7a-acetothio side-chain. The packing of the molecules in the two polymorphs is compared in Fig. 1.9. Both unit cells are orthorhombic but they differ in their b

Form 1

Form 2

Form 1

Figure 1.9 Unit cells of spironolactone.

Reproduced from reference 5 with permission.

Form 2

Figure 1.9 Unit cells of spironolactone.

Reproduced from reference 5 with permission.

Form 1

Form 2

Figure 1.10 Crystal forms of spironolactone.

Reproduced from reference 5 with permission.

Form 2

Figure 1.10 Crystal forms of spironolactone.

Reproduced from reference 5 with permission.

dimensions. The a, b and c axes of Form 1 were found to be 0.998, 3.557 and 0.623 nm respectively, compared with equivalent lengths for Form 2 of 1.058, 1.900 and 1.101 nm. There are also differences in the crystal habits: Form

1 crystals are needle-like, while those of Form

2 are prisms (see Fig. 1.10). The melting points are slightly different: Form 1 melts at 205°C whereas Form 2 has a melting point of 210°C.

Our second example of a drug exhibiting polymorphism is paracetamol (II). This drug is known to exist in two polymorphic forms, monoclinic (Form 1) and orthorhombic (Form 2), of which Form 1 is the more thermo-

Figure 1.11 Scanning electron micrographs showing the crystal habit of (a) Form 1 and (b) Form 2 of paracetamol grown from supersaturated IMS.

Reproduced from reference 6 with permission.

Figure 1.11 Scanning electron micrographs showing the crystal habit of (a) Form 1 and (b) Form 2 of paracetamol grown from supersaturated IMS.